The objective is to study the changes that occur in the hypothalamus, pituitary, gonads and reproductive tract of aging female and male rats, in order to elucidate the mechanisms responsible for loss of reproductive functions. Major emphasis will be placed on studies in female rats that have ceased to exhibit regular estrous cycles and in males that show a significant decrease in serum testosterone levels. The functional capacity of the hypothalamus will be measured by assaying LHRH, turnover of dopamine, norepinephrine and serotonin, and ability to respond to stimuli and drugs that normally produce release of gonadotropins in young mature female rats. Pituitary release of LH, FSH, PRL, GH and TSH will be measured by radio-immunoassay (RIA) in the blood. Changes in ovarian function will be followed by gross and histological examination of the ovaries, by taking daily vaginal smears, and by measuring estrogen and progesterone by RIA in the blood. Attempts will be made to reinitiate estrous cycles and to induce pregnancies, parturition and lactation in old female rats that have ceased to cycle, and to increase serum testosterone levels in old male rats, principally by use of drugs to stimulate hypothalamic function. The functional capacity of the hypothalamo-pituitary system in old rats will be compared with that in young rats by using a variety of challenging stimuli.